The specific aims of the proposed research are to more clearly define the underlying genetic, biochemical, and physiological mechanisms responsible for audiogenic seizure (AS) susceptibility in mice. Recombinant inbred strains and congenic lines of mice, whose AS susceptibility has already been characterized, will be used to study the genetics of AS susceptibility. These groups of mice will be used to distinguish the developmental differences between early-onset and late-onset AS susceptibility. Cross fostering experiments will be used to elucidate the nature of possible maternal effects on late-onset AS susceptibility. In addition, AS susceptible and nonsuceptible mouse strains will be used to determine the importance of serum thyroxine levels and cerebellum growth on the mainifestation of AS susceptibility. Mice susceptible to AS will also be treated with the Beta-adrenergic blocking agent, propranolol, in order to assess the possible involvement of Beta-adrenergic receptors in these seizures. The fatty acid composition (with respect to chain length and degree of unsaturation) of synaptosomal phospholipids will also be studied in the brains of AS susceptible and nonsusceptible mice with the hope of identifying possible differences in membran fludity and permeability between these groups of mice. Since fasting can suppress AS susceptiblity, AS susceptible mice will be used as an animal model to investigate the anticonvulsant mechanisms of fasting. A highly sensitive GLC procedure, employing an electron capture detector, will be used to determine if the concentration of GABA of various brain regions is correlated with AS susceptibility. Because several genetic, developmental, and pharmacological features of AS susceptibility in mice are also shared by certain types of human epilepsies, e.g., febrile, and photosensitive seizures, an understanding of the biochemical defect responsible for AS susceptiblity could help elucidate the underlying biochemical and physiological abnormalities responsible for these types of epilepsies in man.